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Novel, low-molecular-weight fluorescent sensors based on a pyridine–pyridone core structure, which functions as both the chelating part moiety for Zn 2+ and as the fluorophore, were investigated. The length of the methylene spacer between the phenyl ring and the 3-position of the pyridone ring greatly influenced the emission wavelength and intensity upon Zn 2+ binding. 5-Benzyl-4-(methylsulfanyl)-[2,2′-bipyridin]-6(1 H )-one ( 2 ) (MW = 308) with a methylene spacer of n = 1 showed good water solubility, a 30 nm bathochromic shift in its emission wavelength and an 18-fold fluorescence enhancement in response to Zn 2+ . In addition, fluorescence microscopy imaging showed that 2 could be used to detect Zn 2+ in living cells. [ABSTRACT FROM AUTHOR]

A small extent of endogenous labile zinc is involved in many vital physiological roles in living systems. However, its detailed functions have not been fully elucidated. In this study, we developed a novel biheteroaryl-based low molecular weight fluorescent sensor, 3-(phenylsulfonyl)-pyrazine–pyridone (5b), and applied it for the detection of endogenous labile zinc ions from lung cancer cells during apoptosis. The electron-withdrawing property of the sulfonyl group between the phenyl ring as an electron donor and the pyridone ring as a fluorophore inhibited the intramolecular charge transfer state, and the background fluorescence of the sensor was decreased in aqueous media. From the structure–fluorescence relationship analysis of the substituent effects with/without Zn2+, compound 5b acting as a sensor possessed favorable properties, including a longer emission wavelength, a large Stokes shift (over 100 nm), a large fluorescence enhancement in response to Zn2+ under physical conditions, and good cell membrane permeability in living cells. Fluorescence imaging studies of human lung adenocarcinoma cells (A549) undergoing apoptosis revealed that compound 5b could detect endogenous labile zinc ions. These experiments suggested that the low molecular weight compound 5b is a potential fluorescence sensor for Zn2+ toward understanding its functions in living systems. [ABSTRACT FROM AUTHOR]

A high-affinity and low-molecular-weight fluorescent Zn 2+ sensor 1 based on a 2,2′-bipyridine scaffold, which functions as both the chelating moiety for Zn 2+ and the fluorophore, was developed and evaluated in biological applications. Controlling the occurrence of tautomerism of the chelating moiety for Zn 2+ by introducing an amino group at the 6-position of the pyridine ring dramatically increased the binding affinity toward Zn 2+ . Fluorescent sensor 1 exhibited a nanomolar-range dissociation constant ( K d = 2.2 nM), a large Stokes shift (140 nm), and an 8.6-fold turn-on response to Zn 2+ under physiological conditions. Fluorescence images revealed that fluorescent sensor 1 exhibits good properties with respect to aqueous solubility and cell permeability and can quantitatively detect the Zn 2+ levels in living cells. Furthermore, a 65 Zn 2+ radioactive zinc isotope uptake study revealed the real concentration of accumulated Zn 2+ at the detection limit. The novel fluorescent sensor 1 is a promising sensor for use in biological applications. [ABSTRACT FROM AUTHOR]